Temporal changes in the gene signatures of BCG-vaccinated guinea pigs in response to different mycobacterial antigens

Julia A. Tree, Jyoti Patel, Ruth E. Thom, Michael J. Elmore, Hubert Schäfer, Ann Williams, Philip D. Marsh

    Research output: Contribution to journalArticlepeer-review

    6 Citations (Scopus)

    Abstract

    Mycobacterium bovis BCG-vaccination in the guinea pig model of tuberculosis (TB) is sufficiently protective that candidate TB vaccines are judged against this. Little is understood about how the BCG vaccine works and, in the absence of a definitive correlate of protection, it is difficult to interpret the significance of novel vaccine induced host responses. Here an extended custom-made microarray (86 guinea pig genes) was used to dissect temporal changes in BCG-vaccine induced gene signatures to different mycobacterial antigens. Initially at 4. h, pro-inflammatory genes such as IL-1α, IL-1β, IL-8 and GRO were up-regulated (P<0.001) and these were then superseded by IFN-γ and GM-CSF (at 12 and 20. h) post-stimulation, ex vivo with PPD. Similar genes were seen following stimulation with viable BCG but with the addition of IL-23 (P<0.01) after 8. h. Our results suggest that temporal changes in the up- and down-regulation of a variety of genes are required to trigger a successful protective response to TB in guinea pigs. This provides base-line information against which new TB vaccines can be compared.

    Original languageEnglish
    Pages (from-to)7979-7986
    Number of pages8
    JournalVaccine
    Volume28
    Issue number50
    DOIs
    Publication statusPublished - 23 Nov 2010

    Keywords

    • Guinea pig
    • Microarray
    • Tuberculosis

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